Estimation of COVID-19 mRNA Vaccine Effectiveness Against Medically Attended COVID-19 in Pregnancy During Periods of Delta and Omicron Variant Predominance in the United States
Authors: Stephanie J. Schrag, Jennifer R. Verani, Brian E. Dixon, Jessica M. Page, Kristen A. Butterfield, Manjusha Gaglani, Gabriela Vazquez-Benitez, Ousseny Zerbo, Karthik Natarajan, Toan C. Ong, Victoria Lazariu, Suchitra Rao, Ryan Beaver, Sascha R. Ellington, Nicola P. Klein, Stephanie A. Irving, Shaun J. Grannis, Salome Kiduko, Michelle A. Barron, John Midturi, Monica Dickerson, Ned Lewis, Melissa S. Stockwell, Edward Stenehjem, William F. Fadel, Ruth Link-Gelles, Kempapura Murthy, Kristin Goddard, Nancy Grisel, Nimish R. Valvi, Bruce Fireman, Julie Arndorfer, Deepika Konatham, Sarah Ball, Mark G. Thompson, Allison L. Naleway
Journal: JAMA Network Open (2022)

Importance Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed. Objective To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance. Design, Setting, and Participants This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19–like illness (CLI) who underwent SARS-CoV-2 molecular testing. Exposures Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated. Main Outcomes and Measures Estimated VE against laboratory-confirmed COVID-19–associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 − aOR) × 100%. Results Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19–associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19–associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, −49% to 37%), 42% (95% CI, −16% to 72%), 79% (95% CI, 59% to 89%), and −124% (95% CI, −414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, −102% to 93%), 86% (95% CI, 28% to 97%), and −53% (95% CI, −1254% to 83%), respectively. Conclusions and Relevance In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19–associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.